Even in healthy aging, there are many physiological changes. Advanced age is a major risk factor for coronary and peripheral vascular disease. Aging results in significant changes in skeletal muscle, among these is a lower capillary supply, known as capillary rarefaction. A lower skeletal muscle capillary supply is associated with reduced exercise tolerance and reduced insulin sensitivity, which are both risk factors for cardiovascular disease. In general, aging reduces the ability of the organism to respond to different types of stress. Advanced age is associated with a defect in compensatory neovascularization in response to tissue ischemia, possibly through a reduction in vascular endothelial growth factor (VEGF) expression. Recent work suggests that VEGF is important for skeletal muscle capillary maintenance and the angiogenic response to exercise training, a controlled stress that is known to increase VEGF expression. We therefore hypothesize that VEGF expression is lower in old humans. In addition, we hypothesize that in response to the stress of exercise, exercise-induced VEGF expression is reduced in aged humans. To test these hypotheses, we will determine the resting levels of skeletal muscle VEGF from skeletal muscle biopsies in three groups: 18-25 yrs; 45-55 yrs; and 60+ yrs of age. We will then exercise subjects at 50 percent of their maximum for 1 hr on a bicycle ergometer; an intensity and duration that we have shown to increase VEGF mRNA 5-6 fold in young subjects. Isolated mRNA will be analyzed by Northern blot analysis. Proteins will be analyzed by Western blot. Capillarization will be evaluated by morphometric analysis of muscle biopsy samples. Analysis of variance will be used to determine differences between groups and conditions. Data obtained from these studies will provide necessary information for future R01 funding. Findings will be important as little is known concerning the effects of aging on neovascularization potential in humans.